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Xeloda: simplifying the complexity of treatment for metastatic colorectal cancer (MCRC)

Xeloda: simplifying the complexity of treatment for metastatic colorectal cancer (MCRC). Eric Van Cutsem University Hospital Gasthuisberg Leuven, Belgium. Xeloda is an ideal combination partner for cytotoxic and biological agents.

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Xeloda: simplifying the complexity of treatment for metastatic colorectal cancer (MCRC)

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  1. Xeloda: simplifying the complexity of treatment for metastatic colorectal cancer (MCRC) Eric Van Cutsem University Hospital GasthuisbergLeuven, Belgium

  2. Xeloda is an ideal combination partner for cytotoxic and biological agents • Xeloda generates 5-FU preferentially in tumor tissue and has high single-agent, first-line activity • Synergistic antitumor activity in human colon cancer xenografts • Xeloda + oxaliplatin (XELOX)1 • Xeloda + irinotecan (XELIRI)2 • Xeloda + Avastin3 1Cassidy J et al. J Clin Oncol 2004;22:2084–91 2Cao S et al. Clin Colorectal Cancer 2005;4:336–43 3Shen B-Q et al. Proc Am Assoc Cancer Res 2004;45 (Abst 2203)

  3. Xeloda should be thebackbone of CRC therapy • Large body of evidence from phase II and III trials in metastatic and adjuvant CRC • Partially overlapping key toxicities with oxaliplatin and irinotecan; minimal added toxicity with Avastin • Simplifies fluoropyrimidine-containing combination treatment

  4. Replacing infused 5-FU/LV withXeloda: less time wasted per patient • Less time in hospital = more face-to-face time with family 1Köhne CH et al. J Clin Oncol 2003;21:3721–82de Gramont A et al. J Clin Oncol 1997;15:808–15;3Van Cutsem E et al. Br J Cancer 2004;90:1190–7

  5. Clinical case study • 49-year-old woman, pT3N1M0 (3/16) resected sigmoid tumor • Six cycles of adjuvant 5-FU/LV • After 2 years lost 5kg • CT: multiple liver, lung metastases, biopsy confirmed adenocarcinoma • WHO PS = 1; CEA = 140ng/mL; LDH normal; bilirubin normal; alkaline phosphatase normal • Adequate organ function and no comorbidities Liver metastases Lung metastases

  6. Median TTP (months) Median OS (months) 10 8 6 4 2 0 20 15 10 5 0 CAPOX (n=238)2 FUFOX (n=230)2 CAPOX (n=238)2 FUFOX (n=230)2 XELOX (n=96)1 XELOX (n=96)1 Evidence for XELOX: consistently high activity versus 5-FU/oxaliplatin regimens Response rate (%) 60 50 40 30 20 10 0 Oxaliplatin/5-FU (TTD) (n=132)3 CAPOX (n=238)2 FUFOX (n=230)2 XELOX (n=96)1 XELOX (n=128)3 1Cassidy J et al. J Clin Oncol 2004;22:2084–91; 2Arkenau HT et al. J Clin Oncol 2005;23:247s (Abst 3507) 3Sastre J et al. J Clin Oncol 2005;23:252s (Abst 3524)

  7. 2Arkenau HT et al. J Clin Oncol 2005;23:247s (Abst 3507) 3Ducreux M et al. J Clin Oncol 2005;23:270s (Abst 3596) XELOX is well tolerated versus 5-FU/oxaliplatin regimens: phase III evaluation in MCRC 1Sastre J et al. J Clin Oncol 2005;23:252s (Abst 3524) HFS = hand-foot syndrome NR = not reported

  8. XELOX + Avastin:a highly effective combination Response rate (%) 100 80 60 40 20 0 Randomized phase II: TREE-2 study1 Phase II study2 57 52 46 34 mFOLFOX + Avastin bFOL + Avastin XELOX + Avastin Xeloda/oxaliplatin/Avastin 1Hochster HS et al. J Clin Oncol 2005;23:249s (Abst 3515) 2Fernando N et al. J Clin Oncol 2005;23:260s (Abst 3556)

  9. XELOX: limited additional toxicities with Avastin (grade 3/4 adverse events) Patients (%) 35 30 25 20 15 10 5 0 TREE-1: XELOX (n=48) TREE-2: XELOX-Avastin (n=72) NB: lower Xeloda dose HFS Diarrhea Neutropenia Neuro-toxicity Bleeding Venous thromboembolism Hypertension Hochster HS et al. J Clin Oncol 2005;23:249s (Abst 3515)

  10. Median TTP (months) Median OS (months) 10 8 6 4 2 0 30 25 20 15 10 5 0 XELIRI (n=37)3 XELIRI (n=37)3 XELIRI (n=68)2 XELIRI (n=52)1 XELIRI (n=52)1 FOLFIRI (n=145)4 FOLFIRI (n=109)5 FOLFIRI (n=145)4 FOLFIRI (n=109)5 Evidence for XELIRI: consistentlyhigh activity of 3-weekly schedule Response rate (%) 60 50 40 30 20 10 0 XELIRI (n=37)3 XELIRI (n=68)2 XELIRI (n=52)1 FOLFIRI (n=145)4 FOLFIRI (n=109)5 1Patt YZ et al. Ann Oncol 2004;15(Suppl. 3):iii88 (Abst 238P) 2Bajetta E et al. Cancer 2004;100:279–87; 3Borner MM et al. Ann Oncol 2005;16:282–8 4Douillard JY et al. Lancet 2000;355:1041–7; 5Tournigand C et al. J Clin Oncol 2004;22:229–37

  11. Safety of Xeloda- and 5-FU-containing combinations with irinotecan 1Patt YZ et al. Ann Oncol 2004;15(Suppl. 3):iii88 (Abst 238P); 2Borner M et al. Ann Oncol 2005;16:282–83Garcia-Alfonso P et al. J Clin Oncol 2005;23:256s (Abst 3540); 4Ahn J et al. J Clin Oncol 2005;23:299s (Abst 3714)5Köhne C et al. J Clin Oncol 2005;23:252s (Abst 3525); 6Douillard JY et al. Lancet 2000;355:1041–7

  12. 6 7 8 1 2 3 4 5 Case study: clinical outcomeand patient management CT shows PR PS = 0 CEA = 40ng/mL Weight gain 4kg CT confirms PR PS = 0 CEA = 20ng/mL Months Start treatment with XELOX PS = 1 CEA = 140ng/mL Second occurrence grade 2 HFSXeloda interrupted;continued at 75% Grade 2 neurotoxicitypersisted, oxaliplatin discontinued Grade 1diarrhea Grade 2 HFSXeloda interrupted,then reintroducedGrade 2 neurotoxicityoxaliplatin dose reduced

  13. 9 10 12 13 14 15 16 11 Case study: clinical outcomeand patient management CT shows PR PS = 0 CEA = 40ng/mL Weight gain 4kg CT confirms PR PS = 0 CEA = 20ng/mL CTshows PR maintained Months 6 7 8 1 2 3 4 5 July2005 Start treatment with XELOX PS = 1 CEA = 140ng/mL Second occurrence grade 2 HFSXeloda interrupted;continued at 75% Grade 2 neurotoxicitypersisted, oxaliplatin discontinued Grade 1diarrhea Grade 2 HFSXeloda interrupted,then reintroducedGrade 2 neurotoxicityoxaliplatin dose reduced Continueson Xeloda

  14. Xeloda: the backbone of combination treatment for MCRC • XELOX: ideal combination, effective and well tolerated • XELIRI: effective, long-term treatment, with appropriate management of adverse events • Xeloda-based combinations + Avastin: high efficacy and good tolerability • After discontinuation of combination, Xeloda allows continued oral treatment • maximizing response duration first-line • freedom from infusions, continued efficacy with minimal side effects • possibly in combination with Avastin

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